Field of the Invention
The present invention relates to a sensitive diagnostic method for establishing a prostate condition.
Description of the Related Art
Prostate cancer (PCa) remains the second most common cancer worldwide for males with an estimated 900,000 new cases diagnosed in 2008 (Ferlay J, et al. Estimates of cancer incidence and mortality in Europe in 2008, European Journal of Cancer, 2010 46:765-781). According to the Cancer Research UK, PCa is the most common cancer in males in the UK, accounting for 41,000 of new cases of cancer in males every year. In 2008-2010 25% of PCa cases in the UK are diagnosed in men under the age of 65 (CancerStats, Incidence 2009—UK, CRUK May 2012).
Prostate cancer normally causes no symptoms until the cancer has grown large enough to put pressure on the urethra. Symptoms can include weak urinal flow, frequent urination, pain when passing urine etc. Due to the fact that benign prostate conditions such as inflammation, infection and benign prostatic hyperplasia are common in men over the age of 50 and produce similar symptoms, discrimination between prostate cancer and benign prostatic conditions presents a challenge to current diagnostic methods. Currently, there is no single, effective screening test to accurately diagnose prostate cancer in men. The most commonly used PCa diagnostic methods today include the serum prostate-specific antigen analysis (PSA), the digital rectal examination (DRA), and the ultrasound-guided prostate biopsy sampling (Horwich A, et al. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 21 (Supplement 5): v129-v133, 2010). Despite the years of research the specificity and sensitivity of the PSA based multi-step diagnostic approach is still highly inaccurate. For example, in the European Randomized Study 75.9% of men who underwent a biopsy because of an elevated PSA value had no cancer (Schroeder F, et al. Screening and Prostate-Cancer Mortality in a Randomized European Study, N Engl J Med 2009; 360:1320). In addition, a needle biopsy is an invasive and painful procedure with side effects such as prostatitis and blood in urine or semen. Also, many men find the DRA and the needle biopsy embarrassing. In addition to high level of false-positive results, smaller tumors can be missed by current methods with fatal consequences because prostate tumors have the potential to suddenly grow and metastasize.
There is constant search for novel biomarkers to improve specificity of PCa detection. For example, one of such biomarkers currently under clinical investigations is the prostate specific non-coding mRNA marker, PCA3, measured in urine sediment obtained after prostatic massage (Heidenreich A, et al. Guidelines on Prostate Cancer, European Association of Urology 2010). So far, however, none of the investigational biomarkers are being used routinely.
Prostate tissue (Zaichick S and Zaichick V, INAA application in the age dynamics assessment of Br, Ca, Cl, K, Mg, Mn, and Na content in the normal human prostate. J Radioanal Nucl Chem 2011; 288:197-202), expressed prostatic secretions (EPS) (Costello L and Franklin R. Prostatic fluid electrolyte composition for the screening of prostate cancer: a potential solution to a major problem. Prostate Cancer Prostatic Dis 2008; 12(1): 17-24) and seminal fluid (Owen D. and Katz D. A Review of the Physical and Chemical Properties of Human Semen and the Formulation of a Semen Simulant. J Androl 2005:26: 459-469) contain unusually high amounts of electrolytes such as K, Na, Zn, Ca, Mg, Cl, Br and others. The reason for the unusually high metal ion content in normal prostate gland and its excretions is not completely understood, but it was shown that decrease in zinc levels in prostate tissue (Zaichick V, et al. SU997281), prostatic fluid (Zaichick V, et al. Zinc concentration in human prostatic fluid: normal, chronic prostatitis, adenoma and cancer. Int Urol Nephrol 1996:28(5): 687-694) and seminal fluid (Frederickson C. US 2004/229300 A1 and US 2010/0099195 A1; and Leslie C. Costello and Renty B. Franklin, US 2011/0046204 A1) can be used to indicate the risk of prostate cancer. Until now this method has not found practical application.
Thus, so far no reliable method has been developed for prostate cancer detection. Therefore there is a need for a rapid and non-invasive routine prostate cancer test, which can detect PCa in asymptomatic men or discriminate between benign and malignant prostatic conditions in patients with prostatic symptoms.